Trial Outcomes & Findings for PALbociclib CoLlaborative Adjuvant Study (NCT NCT02513394)

Last Updated: 2026-02-10

Results Overview

Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

5796 participants

Primary outcome timeframe

4 years

Results posted on

2026-02-10

Participant Flow

Participant milestones

Participant milestones
Measure	Palbociclib Plus Endocrine Therapy (Arm A) Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Endocrine Therapy Alone (Arm B) Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Study STARTED	2896	2900
Overall Study COMPLETED	2884	2877
Overall Study NOT COMPLETED	12	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Palbociclib Plus Endocrine Therapy (Arm A) Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Endocrine Therapy Alone (Arm B) Standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Study Withdrawal by Subject	11	23
Overall Study Ineligible	1	0

Baseline Characteristics

PALbociclib CoLlaborative Adjuvant Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Total n=5761 Participants Total of all reporting groups
Age, Continuous	52 years n=4 Participants	52 years n=4 Participants	52 years n=8 Participants
Sex: Female, Male Female	2867 Participants n=4 Participants	2858 Participants n=4 Participants	5725 Participants n=8 Participants
Sex: Female, Male Male	17 Participants n=4 Participants	19 Participants n=4 Participants	36 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	138 Participants n=4 Participants	127 Participants n=4 Participants	265 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2504 Participants n=4 Participants	2532 Participants n=4 Participants	5036 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	242 Participants n=4 Participants	218 Participants n=4 Participants	460 Participants n=8 Participants
Race/Ethnicity, Customized Race · Asain	138 Participants n=4 Participants	141 Participants n=4 Participants	279 Participants n=8 Participants
Race/Ethnicity, Customized Race · Black or African American/African Heritage	74 Participants n=4 Participants	75 Participants n=4 Participants	149 Participants n=8 Participants
Race/Ethnicity, Customized Race · White	2521 Participants n=4 Participants	2498 Participants n=4 Participants	5019 Participants n=8 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or other Pacific Islander	4 Participants n=4 Participants	8 Participants n=4 Participants	12 Participants n=8 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	14 Participants n=4 Participants	22 Participants n=4 Participants	36 Participants n=8 Participants
Race/Ethnicity, Customized Race · Other	37 Participants n=4 Participants	36 Participants n=4 Participants	73 Participants n=8 Participants
Race/Ethnicity, Customized Race · Unknown	96 Participants n=4 Participants	97 Participants n=4 Participants	193 Participants n=8 Participants

PRIMARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
Invasive Disease Free Survival (iDFS)	84.5 percentage of participants	84.2 percentage of participants

SECONDARY outcome

Timeframe: 4 years

Invasive disease-free survival (iDFS, excluding second primary invasive cancers of non-breast origin) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS excluding second primary invasive cancers of non-breast origin is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause. Second primary invasive cancers of non-breast origin will not be considered as events for this endpoint. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.

Outcome measures

Outcome measures
Measure	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin.	86.0 percentage of patients	85.4 percentage of patients

SECONDARY outcome

Timeframe: 4 years

Compare time to distant recurrence-free survival (DRFS). Distant recurrence is defined according to STEEP criteria as the time from randomization to the date of the first event: distant recurrence or death from any cause. Patients with a locoregional recurrence will continue to be followed for DRFS. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, or death whichever came first. Direct comparison between arms used time to DRFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered DRFS at 4 years is reported.

Outcome measures

Outcome measures
Measure	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
Distant Recurrence-free Survival (DRFS)	87.8 percentage of patients	86.2 percentage of patients

SECONDARY outcome

Timeframe: 4 years

Compare overall survival (OS). Overall survival is defined as the time period between randomization and death. Surviving patients classified as lost-to-follow up or having withdrawn consent to be followed will be censored at their date of last contact or withdrawal of consent to be followed, whichever occurs first.

Outcome measures

Outcome measures
Measure	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
Overall Survival (OS)	95.2 percentage of patients	93.8 percentage of patients

SECONDARY outcome

Timeframe: 4 years

Compare locoregional recurrence-free survival (LRRFS). LRRFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, or death from any cause. Patients with second primary invasive cancers of non-breast origin or distant recurrence will be censored at the date of diagnosis. Surviving patients who are event-free will be censored at: the date of last disease assessment, or withdrawal of consent to be followed, whichever occurs first.

Outcome measures

Outcome measures
Measure	Endocrine Therapy Alone (Arm B) n=2877 Participants Standard adjuvant endocrine therapy for a duration of at least 5 years.	Palbociclib Plus Endocrine Therapy (Arm A) n=2884 Participants Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.
Locoregional Recurrences-free Survival (LRRFS)	95.4 percentage of patients	96.8 percentage of patients

Adverse Events

Palbociclib Plus Endocrine Therapy (Arm A)

Serious events: 369 serious events

Other events: 2824 other events

Deaths: 99 deaths

Endocrine Therapy Alone (Arm B)

Serious events: 229 serious events

Other events: 2600 other events

Deaths: 76 deaths

Serious adverse events

Other adverse events

Additional Information

Erica L. Mayer, MD, MPH

Dana-Farber Cancer Institute

Phone: 617-632-3800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Palbociclib Plus Endocrine Therapy (Arm A) n=2841 participants at risk Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Endocrine Therapy Alone (Arm B) n=2902 participants at risk Standard adjuvant endocrine therapy for a duration of at least 5 years.
Renal and urinary disorders Ureterolithiasis	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Adnexa uteri cyst	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Breast calcifications	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Breast cyst	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Breast haematoma	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Breast necrosis	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.07% 2/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Breast swelling	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Cervical cyst	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Endometrial disorder	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Endometrial hyperplasia	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.07% 2/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Endometrial hypertrophy	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Endometrial thickening	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Endometriosis	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Ovarian cyst	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Uterine polyp	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Uterine prolapse	0.07% 2/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Vaginal haematoma	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Asthma-chronic obstructive pulmonary disease overlap syndrome	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.07% 2/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.07% 2/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Laryngeal stenosis	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.07% 2/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pleurisy	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.14% 4/2841 • Number of events 4 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.46% 13/2841 • Number of events 13 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.17% 5/2902 • Number of events 5 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Pulmonary sarcoidosis	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.04% 1/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Vocal cord dysfunction	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Respiratory, thoracic and mediastinal disorders Vocal cord polyp	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Skin and subcutaneous tissue disorders Keloid scar	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).

Other adverse events
Measure	Palbociclib Plus Endocrine Therapy (Arm A) n=2841 participants at risk Palbociclib at a dose of 125 mg orally once daily, Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle for a total duration of 2 years, in addition to standard adjuvant endocrine therapy for a duration of at least 5 years.	Endocrine Therapy Alone (Arm B) n=2902 participants at risk Standard adjuvant endocrine therapy for a duration of at least 5 years.
Investigations Liver function test increased	0.14% 4/2841 • Number of events 4 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.28% 8/2902 • Number of events 8 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Low density lipoprotein increased	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Lymph node palpable	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Lymphocyte count	0.04% 1/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Lymphocyte count decreased	11.2% 317/2841 • Number of events 926 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	3.4% 100/2902 • Number of events 161 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Lymphocyte count increased	0.25% 7/2841 • Number of events 7 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Lymphocyte percentage increased	0.04% 1/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin concentration	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin concentration abnormal	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin concentration decreased	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin concentration increased	0.11% 3/2841 • Number of events 3 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin decreased	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell haemoglobin increased	0.39% 11/2841 • Number of events 14 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell volume	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell volume abnormal	0.28% 8/2841 • Number of events 8 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell volume decreased	0.07% 2/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean cell volume increased	0.49% 14/2841 • Number of events 17 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean platelet volume decreased	0.18% 5/2841 • Number of events 6 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.07% 2/2902 • Number of events 3 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Mean platelet volume increased	0.04% 1/2841 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Monocyte count decreased	0.46% 13/2841 • Number of events 24 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Monocyte count increased	0.28% 8/2841 • Number of events 9 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Monocyte percentage decreased	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Neutrophil count	0.32% 9/2841 • Number of events 13 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Neutrophil count abnormal	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Neutrophil count decreased	47.3% 1344/2841 • Number of events 6144 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	2.3% 67/2902 • Number of events 109 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Neutrophil count increased	0.14% 4/2841 • Number of events 5 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.21% 6/2902 • Number of events 6 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Investigations Neutrophil percentage decreased	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Psychiatric disorders Agitation Mood Disturbance	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Ear and labyrinth disorders Veritgo	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Agranulocytosis	0.11% 3/2841 • Number of events 3 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Anaemia	22.3% 634/2841 • Number of events 1161 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	5.1% 147/2902 • Number of events 211 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Anaemia macrocytic	0.14% 4/2841 • Number of events 6 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Anaemia vitamin B12 deficiency	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Blood disorder	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Bone marrow oedema	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Eosinophilia	0.00% 0/2841 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.07% 2/2902 • Number of events 2 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Febrile neutropenia	0.56% 16/2841 • Number of events 16 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Haematotoxicity	0.04% 1/2841 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Haemorrhagic diathesis	0.11% 3/2841 • Number of events 3 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.00% 0/2902 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).
Blood and lymphatic system disorders Increased tendency to bruise	0.11% 3/2841 • Number of events 3 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).	0.03% 1/2902 • Number of events 1 • 4 years The safety analysis is conducted in the "as-treated" population. Patients randomly assigned to the Arm A who never received Palbociclib but received endocrine therapy (N=36) were included in Arm B for the safety analyses. Thus, the safety analysis included 2841 patients who received at least one dose of Palbociclib plus endocrine therapy and 2902 patients who received endocrine therapy (which included 36 patients from Arm A who received endocrine therapy only).